Molecular Analysis of Arabidopsis Circadian Regulation

拟南芥昼夜节律调节的分子分析

基本信息

批准号：
8230455
负责人：
Stacey L. Harmer
金额：
$ 27.79万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2013-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Circadian rhythms, roughly 24-hour rhythms in physiology and behavior, are widespread in nature and can be found in many plants and animals. Disruption of circadian rhythms has been linked to human health disorders ranging from jet lag to sleep and mood disorders and even to cancer. In eukaryotes, the circadian clocks that drive these rhythms are composed of networks of interlocked transcriptional feedback loops, in which positive factors induce the expression of negative factors that in turn repress expression of the positive factors. Although individual clock components are not conserved across kingdoms, clear analogies can be drawn between the organization of the circadian system and the `wiring' of the central clock, or oscillator, between disparate organisms. A fundamental understanding of how the circadian clock works in a variety of model systems will lead to new insights into the functioning of the human circadian system and its role in human health and disease. The long-term goal of the proposed research is to better understand the molecular basis of circadian rhythms in eukaryotes. These studies will be performed in Arabidopsis thaliana, a model organism with extensive genetic and genomic resources that is well-suited to circadian research. Some predicted components of the Arabidopsis central clock have not yet been identified, the biochemical functions of many known clock genes have not been determined, and it is not understood how the clock regulates growth and development. The proposed studies will use genetic, genomic, and biochemical techniques to address these fundamental questions. First, the molecular function of a clock-associated protein that is highly conserved across eukaryotes will be determined by a combination of genetic and biochemical studies in Arabidopsis and fission yeast. Second, a gene that acts close to the central clock will be cloned and characterized. Finally, the targets of a clock-regulated transcription factor that modulates the central clock and regulates organ size will be identified. These studies will yield important insights into the workings of the circadian clock and how it regulates growth and development in a complex eukaryote, information that ultimately may be used to improve human health through treatment of circadian disorders. PUBLIC HEALTH RELEVANCE: Almost all organisms possess an internal clock that generates roughly 24-hour rhythms in physiology or behavior. Disruption of this circadian clock in humans has serious negative consequences, causing sleep and mood disorders and perhaps even contributing to diseases such as cancer. To better understand the molecular basis of circadian rhythms, we are carrying out extensive genetic, biochemical, and genomic studies on the model organism Arabidopsis thaliana.

描述（由申请人提供）：昼夜节律，大约24小时的生理和行为节奏，在自然界中广泛存在，可以在许多植物和动物中找到。昼夜节律的破坏与从喷气滞后到睡眠和情绪障碍甚至癌症的人类健康障碍有关。在真核生物中，驱动这些节奏的昼夜节律是由互锁转录反馈循环网络组成的，其中阳性因素诱导负面因素的表达，而负面因素反过来抑制了积极因素的表达。尽管单个时钟组件在整个王国之间并非保守，但是在昼夜节律系统的组织和中央时钟或振荡器之间的“接线”之间可以绘制明显的类比。对昼夜节律如何在各种模型系统中运作的基本了解将导致对人类昼夜节律系统功能及其在人类健康和疾病中的作用的新见解。拟议的研究的长期目标是更好地了解真核生物中昼夜节律的分子基础。这些研究将在拟南芥（Thaliana）中进行，这是一种模型生物体，具有广泛的遗传和基因组资源，非常适合昼夜研究。尚未确定拟南芥中心时钟的一些预测组成部分，尚未确定许多已知时钟基因的生化功能，也不理解时钟如何调节生长和发展。拟议的研究将使用遗传，基因组和生化技术来解决这些基本问题。首先，在跨真核生物中高度保守的时钟相关蛋白的分子功能将由拟南芥和裂变酵母中的遗传学和生化研究的组合确定。其次，一个接近中心时钟的基因将被克隆和表征。最后，将确定调节中心时钟并调节器官大小的时钟调节转录因子的目标。这些研究将对昼夜节律时钟的运作以及它如何调节复杂的真核生物的生长和发展产生重要的见解，这些信息最终可以通过治疗昼夜节律疾病来改善人类健康。公共卫生相关性：几乎所有生物具有内部时钟，大约产生了生理或行为的24小时节奏。这种昼夜节律在人类中的破坏会带来严重的负面影响，导致睡眠和情绪障碍，甚至导致诸如癌症之类的疾病。为了更好地了解昼夜节律的分子基础，我们正在对模型有机体拟南芥进行广泛的遗传，生化和基因组研究。